1. Technical Field of the Invention
The present invention relates to the cosmetic administration of coumarin and derivatives thereof, butylated hydroxyanisole and ethoxyquine for treating canities.
2. Description of Background and/or Related and/or Prior Art
The hair follicle is a tubular invagination of the epidermis which extends to the deep layers of the dermis. The lower part, or hair bulb, itself comprises an invagination in which the dermal papilla is located. The lower part of the bulb is an area of cell proliferation where the precursors of the keratinized cells that form hair are found. The ascending cells derived from these precursors become gradually keratinized in the upper part of the bulb, and this assembly of keratinized cells will form the hair shaft.
The color of head hair and of body hair depends especially on the presence, in variable amounts and ratios, of two groups of melanins: eumelanins (brown and black pigments) and pheomelanins (red and yellow pigments). The pigmentation of head hair and body hair requires the presence of melanocytes in the bulb of the hair follicle. These melanocytes are in an active state, that is to say that they synthesize melanins. These pigments are transmitted to the keratinocytes intended to form the hair shaft, which will result in the growth of a pigmented head hair or body hair. This structure is hereinafter called “follicular pigmentation unit”.
In mammals, melanogenesis involves at least three enzymes: tyrosinase, DOPAchrome tautomerase (TRP-2, for Tyronsinase Related Protein 2) and DHICAoxidase (TRP-1, for Tyrosinase Related Protein 1).
Tyrosinase is the enzyme that initiates the biosynthesis of melanins. It is also described as being the limiting enzyme of melanogenesis.
TRP-2 catalyzes the tautomerization of DOPAchrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA). In the absence of TRP-2, the DOPAchrome undergoes a spontaneous decarboxylation to form 5,6-dihydroxyindole (DHI).
DHICA and DHI are both pigment precursors, TRP-1 oxidizes DHICA molecules to form quinine derivatives (Pawelek, J. M. and Chakraborty A. K., “The enzymology of melanogenesis” in “The Pigmentary System: Physiology and Pathophysiology”, by Nordlund, J. J., Boissy, R. E., Hearing, V. J., King, R. A., Ortonne, J-P., New York, Oxford University Press, 1998, p. 391-400).
The three enzymes, tyrosinase, TRP-2 and TRP-1, appear to be specifically involved in melanogenesis. In addition, the activity of these three enzymes has been described as being necessary for the maximum activity of biosynthesis of eumelanins.
Head hair and body hair undergo a cycle. This cycle comprises a growth phase (anagen phase), a degenerative phase (catagen phase) and a rest phase (telogen phase) following which a new anagen phase will develop. Due to this hair cycle, and unlike the epidermal pigmentation unit, the follicular pigmentation unit must also be cyclically renewed.
Canities (natural hair whitening) is linked to a specific and gradual depletion of the hair melanocytes that affects both the hair bulb melanocytes and the melanocyte precursor cells (Commo, et al., Br. J. Dermatol., 2004, 150, 435-443). Other cell types present in the hair follicles are not affected. In addition, this depletion of melanocytes is not observed in the epidermis. The cause of this gradual and specific depletion of melanocytes and melanocyte precursors in the hair follicle has not been identified to date.
It therefore appears necessary to combat the disappearance of melanocytes from human hair follicles, a process that affects both the active melanocytes of the bulbs and the quiescent melanocytes of the upper region of the hair follicles, in order to combat canities.
The assignee hereof has identified a means of combating hair whitening by acting on the TRP-2 enzyme (WO 03/103568), especially by increasing the level of GSH. Indeed, it has been demonstrated that the expression of the TRP-2 enzyme is correlated with a higher level of GSH in the melanocytes, the expression of TRP-2 induces an increase in the level of GSH in the melanocytes. Thus, in the melanocytes which do not express TRP-2 (for example, the melanocyte precursors of hair), there is a low level of GSH in comparison with the melanocytes that express the TRP-2 enzyme (for example, all the skin melanocytes).
The assignee hereof has therefore identified a novel target for the treatment of canities, more particularly it has demonstrated that the compounds capable of increasing the level of GSH in the melanocytes that are deficient in TRP-2 increase the viability of these melanocytes, decrease hair whitening and lead, unlike their depigmenting effect described in the literature, to the restoring of hair pigmentation (FR 04/13756).